Hide Michihiro, Ohsawa Isao, Nurse Christina, Yu Ming
Department of Dermatology, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan.
Department of Dermatology, Hiroshima University, Hiroshima, Japan.
J Dermatol. 2023 Nov;50(11):1381-1391. doi: 10.1111/1346-8138.16909. Epub 2023 Aug 14.
The safety and efficacy of lanadelumab for the prevention of hereditary angioedema (HAE) attacks have not been studied in Japanese patients. We report outcomes from a phase 3, multicenter, open-label study (NCT04180163) of lanadelumab in Japanese patients with HAE. Japanese patients with HAE aged ≥12 years with ≥1 investigator-confirmed HAE attack during the 4-week run-in baseline period were enrolled into the study and received lanadelumab 300 mg every 2 weeks subcutaneously for 52 weeks. Dosing could be reduced to 300 mg every 4 weeks during the second 26-week treatment period if patients had well-controlled symptoms (e.g., attack-free) for 6 months. The primary efficacy endpoint was no investigator-confirmed HAE attacks (attack-free status) during days 0-182. Other outcomes included the rate of investigator-confirmed HAE attacks per month (28 days) and lanadelumab safety. Twelve patients (mean ± SD age 41.9 ± 12.4 years) were enrolled. During the first 26 weeks (days 0-182), five (41.7%) patients were attack-free. The mean ± SD HAE attack rate per month decreased by 74.0%, from 3.8 ± 2.4 during baseline to 1.2 ± 2.6 during the overall 52-week treatment period. There were no deaths or discontinuations due to treatment-emergent adverse events (TEAEs), no severe or serious TEAEs related to lanadelumab, and no positive anti-drug antibody results. The most frequent TEAEs were injection-site reactions (37 events in six patients). Most of the injection-site reaction adverse events were mild in severity. Results of this study support the findings from two global phase 3 studies for lanadelumab use as prophylactic therapy in Japanese patients with HAE.
在日本患者中，尚未对拉那度单抗预防遗传性血管性水肿（HAE）发作的安全性和有效性进行研究。我们报告了一项针对日本HAE患者的3期、多中心、开放标签研究（NCT04180163）的结果。年龄≥12岁、在为期4周的导入基线期内有≥1次经研究者确认的HAE发作的日本HAE患者被纳入该研究，并接受皮下注射拉那度单抗300mg，每2周一次，共52周。如果患者症状得到良好控制（如无发作）达6个月，则在第二个26周治疗期内给药频率可减至每4周300mg。主要疗效终点是在第0至182天期间无经研究者确认的HAE发作（无发作状态）。其他结果包括每月（28天）经研究者确认的HAE发作率以及拉那度单抗的安全性。12名患者（平均±标准差年龄41.9±12.4岁）被纳入研究。在最初的26周（第0至182天），5名（41.7%）患者无发作。每月的平均±标准差HAE发作率下降了74.0%，从基线期的3.8±2.4降至整个52周治疗期的1.2±2.6。没有因治疗中出现的不良事件（TEAE）导致死亡或停药，没有与拉那度单抗相关的严重或重度TEAE，也没有抗药物抗体阳性结果。最常见的TEAE是注射部位反应（6名患者出现37次）。大多数注射部位反应不良事件的严重程度为轻度。本研究结果支持两项全球3期研究的结果，即拉那度单抗可作为日本HAE患者的预防性治疗药物。
